K. Kjaer

IT University of Copenhagen, København, Capital Region, Denmark

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Publications (96)351.71 Total impact

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    ABSTRACT: Autosomal recessive primary microcephaly (MCPH) is caused by mutations in at least eight different genes involved either in cell division or DNA repair. Most mutations are identified in consanguine families from Pakistan, Iran and India. To further assess their genetic heterogeneity and mutational spectra, we have analyzed 57 consanguine Pakistani MCPH families. In 34 MCPH families, we detected linkage to five out of the eight well-characterized disease loci and identified mutations in 27 families, leaving seven families without mutations in the coding exons of the presumably underlying MCPH genes. In the MCPH cohort 23 families could not be linked to any of the known loci, pointing to remarkable locus heterogeneity. The majority of mutations were found in ASPM followed by WDR62, CENPJ, CEP152 and MCPH1. One ASPM mutation (p.Trp1326*) was found in as many as eight families suggesting a Pakistani founder mutation. One third of the families were linked to ASPM followed by WDR62 confirming previous data. We identified three novel ASPM mutations, four novel WDR62 mutations, one novel MCPH1 mutation and two novel CEP152 mutations. CEP152 mutations have not been described before in the Pakistani population.
    No preview · Article · Jul 2012 · Clinical Genetics
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    ABSTRACT: Grazing incidence x-ray diffraction (GIXD) measurements were performed to determine the effects of SP-B 1.35, the N-terminus peptide of lung surfactant specific protein SP-B, on the structure of palmitic acid (PA) monolayers. In-plane diffraction shows that the peptide fluidizes a portion of the monolayer, but does not affect the packing of the residual ordered phase. This implies that the peptide resides in the disordered phase, and that the ordered phase is essentially pure lipid. The quantitative insights afforded by this study lead to a better understanding of the lipid/protein interactions found in lung surfactant systems.
    No preview · Article · Jan 2011 · MRS Online Proceeding Library
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    ABSTRACT: X-ray scattering experiments on mixed films of cholesterol and phospholipids at air-water and Si solid-water interfaces were undertaken to glean information on pathological crystallization of cholesterol bilayers. Grazing-incidence X-ray diffraction patterns at the air-water interface of various cholesterol:dipalmitoyl-phosphatidylcholine (Ch:DPPC) monolayer mixtures compressed beyond monolayer collapse yielded the established 10 x 7.5 Ų Ch bilayer motif, for Ch:DPPC molar ratios higher than 2.5:1. Attempts to obtain a diffraction signal from various Ch:phospholipid film mixtures at the Si solid-water interface, indicative of the presence of the Ch bilayer motif, were unsuccessful. Only after removal of sufficient water from the cell was a weak diffraction signal obtained suggestive of a cholesterol film two bilayers thick. Off-specular X-ray reflectivity measurements made on a 1.75:1 mixture of Ch and bovine cardiac phosphatidylcholine (BCPC) deposited as a bilayer on a Si wafer and placed in a cell filled with water yielded positive results. The derived electron density profile showed the presence of a bilayer mixture consistent with a phase separation of cholesterol and BCPC, and possible formation of a crystalline cholesterol bilayer within the hydrated mixed bilayer, but not a proof thereof.
    No preview · Article · Aug 2009 · The European Physical Journal E
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    ABSTRACT: Phospholipid monolayers at the air-water interface have been studied by synchrotron x-ray reflection methods. The range of momentum transfers (perpendicular to the surface) exceeded 2π/(layer thickness) thus yielding information about the density distribution across the layer. Data for a monolayer of L-α-dipalmitoylphosphatidylcholine (DPPC) in the solid phase (surface pressure 40 mN/m) are interpreted in terms of a simple model of the density with adjustable values for the densities and the projected lengths of the aliphatic tail and the polar head as well as an overall Gaussian smearing of the densities. We find that the tails are close-packed but uniformly tilted 30° relative to the interface normal.
    No preview · Article · Jul 2007 · EPL (Europhysics Letters)
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    ABSTRACT: Characterisation of disease associated balanced chromosome rearrangements is a promising starting point in the search for candidate genes and regulatory elements. We have identified and investigated three patients with limb abnormalities and breakpoints involving chromosome 2q31. Patient 1 with severe brachydactyly and syndactyly, mental retardation, hypoplasia of the cerebellum, scoliosis, and ectopic anus, carries a balanced t(2;10)(q31.1;q26.3) translocation. Patient 2, with translocation t(2;10)(q31.1;q23.33), has aplasia of the ulna, shortening of the radius, finger anomalies, and scoliosis. Patient 3 carries a pericentric inversion of chromosome 2, inv(2)(p15q31). Her phenotype is characterised by bilateral aplasia of the fibula and the radius, bilateral hypoplasia of the ulna, unossified carpal bones, and hypoplasia and dislocation of both tibiae. By fluorescence in situ hybridisation, we have mapped the breakpoints to intervals of approximately 170 kb or less. None of the three 2q31 breakpoints, which all mapped close to the HOXD cluster, disrupted any known genes. Hoxd gene expression in the mouse is regulated by cis-acting DNA elements acting over distances of several hundred kilobases. Moreover, Hoxd genes play an established role in bone development. It is therefore very likely that the three rearrangements disturb normal HOXD gene regulation by position effects.
    Full-text · Article · Mar 2006 · Journal of Medical Genetics
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    ABSTRACT: Using neutron/X-ray reflectivity and X-ray grazing incidence diffraction (GID), we have characterized the structure of mixed DPPE:GM(1) lipid monolayers before and during the binding of cholera toxin (CTAB(5)) or its B subunit (CTB(5)). Structural parameters such as the density and thickness of the lipid layer, extension of the GM(1) oligosaccharide headgroup, and orientation and position of the protein upon binding are reported. Both CTAB(5) and CTB(5) were measured to have approximately 50% coverage when bound to the lipid monolayer. X-ray GID experiments show that both the lipid monolayer and the cholera toxin layer are crystalline. The effects of X-ray beam damage have been assessed and the monolayer/toxin structure does not change with time after protein binding has saturated.
    Full-text · Article · Mar 2005 · Colloids and surfaces B: Biointerfaces
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    ABSTRACT: The surface-pressure-induced layering transition of a 2D nematic-like cyclolinear polyorganosiloxane that consists of six-membered rings of silicon and oxygen joined by oxygen bridges and that has phenyl side groups (CL-PMPhSi) is observed and characterized by film balance measurements, Brewster angle microscopy (BAM), and grazing incidence X-ray diffraction (GIXD) at the air/water interface. In the uncompressed state, A ≤ 95 Å2/monomer and π ≈ 0, BAM images demonstrate partial surface coverage by solidlike birefringent islands, supporting the previously suggested model of extended aligned polymer chains lying parallel to the water surface in a quasi-two-dimensional “nematic-like” liquid-crystalline arrangement. Further compression, A ≤ 95 Å2/monomer, leads to a complete and uniform monolayer coverage of the surface followed by layer-by layer growth visible as stepwise increasing surface pressure. GIXD reveal one diffraction peak for monolayer as well as multilayer samples of CL-PMPhSi with a d-spacing of d = (10.5 ± 0.1) Å. The maximum Bragg rod intensity is observed at qz ≈ 0 for the monolayer but moved to a well-defined nonzero qz value for the multilayer samples. We infer that there are planes in the structure of the CL-PMPhSi multilayers tilted by ca. 27° from the surface normal. For both mono- and multilayers, the analysis of the observed GIXD peak widths indicates that the extent of the lateral positional correlation between parallel chains ranges from about 12 for the monolayer to about 30 interchain distances in multilayers, implying some mesoscale order similar to a quasi-long-range order. Analysis of the Bragg rods allowed us to estimate the thickness of the monolayer and multilayers. Comparison of the data with independent results of molecular modeling, X-ray reflectivity, and atomic force microscopy gave very good agreement. As a result of the analysis we conclude that both in-plane and out-of-plane GIXD data reveal a high degree of stable structural order of the CL-PMPhSi films.
    Full-text · Article · May 2004 · Macromolecules
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    ABSTRACT: The surface pressure induced transitions of Langmuir monolayers to multilayers of 2D-nematic-like cyclolinear polyorganosiloxanes at the air/water interface is observed and characterized by film balance measurements, Brewster angle microscopy (BAM), surface sensitive synchrotron X-ray diffraction (GIXD) and reflectivity (XR) with a liquid surface diffractometer and scanning force microscopy (SFM) after deposition onto solid surfaces. Surface pressure (π) versus surface area (A) isotherm data for these polymers show several steps and plateaus and this had been assumed to indicate the formation of multilayers with distinct layer thickness consisting of 1, 2, 3, etc. (up to seven) layers. For the Langmuir monolayers (LM's) and multilayers the observed single GIXD peak allowed to estimate: i) the inter-chain distance in planes, ii) the extent of the lateral positional correlation between parallel chains, iii) the thickness of the multilayers and separate monolayers. The results obtained with XR reveal that the multilayers have a very uniform layer thickness and that there is a significant degree of structural order in the packing of these polymers in the multilayers in a direction perpendicular to the polymer axis, i.e. two-dimensional structural order (in and out of plane). SFM performed on the Langmuir monolayers and bi-layers transferred to solid supports showed relatively homogeneous covering. Some possible application of the multi-layers is discussed.
    No preview · Article · Jan 2004 · Nonlinear Optics Quantum Optics
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    ABSTRACT: Siloxane polymers self-organized into nanostructures with controllable distinct thicknesses from 1 to at least 6 molecular layers, ie, 1-6 nm, are investigated. Macroscopic manipulation of the surface pressure for these ultrathin films leads to an architecture with a distinct layer thickness and a highly ordered structure as demonstrated by synchrotron X-ray reflectivity measurements performed in situ at the air/water interface. An atactic polymer of cyclolinear methylphenylsiloxane (CL-PMPhSi) that consists of monomer rings formed by six silicon ...
    Full-text · Article · Sep 2003 · Macromolecules
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    ABSTRACT: A strong Bragg peak, attributed to regular corrugation in a crystalline film, was detected in a series of self-assembled supramolecular complexes of bifunctional bolaamphiphiles of different lengths, with divalent ions of Pb and Cu, at the airaqueous interface. This peak has a d spacing half that of the proposed corrugation-repeat length of ca. 82 Å, which is not a multiple of the long lattice spacing of the crystalline structure, and is susceptible to film compression. This corrugation is interpreted in terms of unfavorable interactions between the polar aqueous surface and the nonpolar hydrocarbon part of the bolaamphiphiles. To establish the nature of the corrugation, grazing-incidence X-ray diffraction and specular X-ray reflectivity with synchrotron radiation were applied, as well as scanning force microscopy of films deposited on mica.
    No preview · Article · Aug 2003 · Helvetica Chimica Acta
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    ABSTRACT: The advent of intense X-rays from synchrotron sources made possible to probe, at the molecular level, the structural aspects of self-assemblies generated at interfaces. Here we present the two-dimensional (2-D) packing arrangements of two-, three- and multi-component organo-metallic self-assemblies formed via interfacial reaction at the air–aqueous solution interface, as determined by grazing incidence X-ray diffraction (GIXD) and X-ray specular reflectivity techniques. GIXD yields structural information on the crystalline part of the Langmuir film, including the ions and counterions lateral order. Specular reflectivity yields the electron density profile of the film in the direction normal to the air–solution interface and, by modeling, gives independent information on the structure of both crystalline and amorphous parts of the film. In particular, we focus on the following systems: ordering of metal ions bound to the polar head groups of amphipilic molecules; use of bolaamphiphiles to generate oriented thin films with metal ions arranged in periodic layers; delineation of differences in the lateral organization of metal ions at interfaces as induced by racemates and enantiomerically pure amphiphiles; organization of ionophores in the presence of metal ions in membrane-like environment; self-assembly of 2×2 and 3×3 silver(I) grid-type complexes generated at the air–solution interface.
    No preview · Article · Aug 2002 · Colloids and Surfaces A Physicochemical and Engineering Aspects

  • No preview · Article · Aug 2002 · Acta Crystallographica Section A Foundations of Crystallography
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    J Majewski · T L Kuhl · K Kjaer · G S Smith
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    ABSTRACT: Using synchrotron grazing-incidence x-ray diffraction (GIXD) and reflectivity, the in-plane and out-of-plane structure of mixed ganglioside-phospholipid monolayers was investigated at the air-water interface. Mixed monolayers of 0, 5, 10, 20, and 100 mol% ganglioside GM(1) and the phospholipid dipalmitoylphosphatidylethanolamine (DPPE) were studied in the solid phase at 23 degrees C and a surface pressure of 45 mN/m. At these concentrations and conditions the two components do not phase-separate and no evidence for domain formation was observed. X-ray scattering measurements reveal that GM(1) is accommodated within the host DPPE monolayer and does not distort the hexagonal in-plane unit cell or out-of-plane two-dimensional (2-D) packing compared with a pure DPPE monolayer. The oligosaccharide headgroups were found to extend normally from the monolayer surface, and the incorporation of these glycolipids into DPPE monolayers did not affect hydrocarbon tail packing (fluidization or condensation of the hydrocarbon region). This is in contrast to previous investigations of lipopolymer-lipid mixtures, where the packing structure of phospholipid monolayers was greatly altered by the inclusion of lipids bearing hydrophilic polymer groups. Indeed, the lack of packing disruptions by the oligosaccharide groups indicates that protein-GM(1) interactions, including binding, insertion, chain fluidization, and domain formation (lipid rafts), can be studied in 2-D monolayers using scattering techniques.
    Full-text · Article · Dec 2001 · Biophysical Journal
  • M Weygand · K. Kjaer · P B Howes · B. Wetzer · D Pum · U B Sleytr · M. Losche

    No preview · Article · Nov 2001
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    ABSTRACT: Five bifunctional α-amino acid-ε-carboxy bolaamphiphiles [(2-R,S, or RS)−(HOOC)−(CH2)m-CONH−(CH2)n-CH(COOH)(NH2) m=20,22, n=3,4 labeled (l), (d,l)-C22Orn (l), (d), (d,l)-C22Lys, (d,l)-C24Lys respectively] were synthesized. These molecules were deposited on different aqueous subphases, and studied by means of grazing incidence X-ray diffraction (GIXD). On deionized water, the bolaamphiphiles (d,l)-C22Lys yield a mixture of crystallites:  both a monolayer, in which the chains are tilted from the normal, and a multilayer in which the molecules lie parallel to the water. On the other hand, when deposited on mono- or bi-metal ionic subphases, they self-assemble into crystalline multilayer films in which the molecules lie parallel to the aqueous solution surface, linked head-to-head and tail-to-tail in the form of extended chains. The latter are juxtaposed such that the metal ions form sheets separated by the organic molecules, aligned perpendicular to the plane of the aqueous solution. Deposition of either the enantiomerically pure or racemic bifunctional bolaamphiphiles on an aqueous solution of mixed Cu(Acetate)2 and Pb(Acetate)2, yields self-assembled crystalline films composed of the two different metal cations, arranged in alternating sheets, separated by the organic spacer. Both GIXD and X-ray-photoelectric-spectroscopy (XPS) studies (after deposition on solid support) demonstrate that the structures of these films differ form the ones formed on either pure Pb(Ac)2 or on Cu(Ac)2 solutions, thus excluding the simultaneous formation of the two monometallic crystalline phases.
    No preview · Article · Oct 2001 · The Journal of Physical Chemistry B
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    ABSTRACT: Cholesterol and some cholesterol-like derivatives such as stigma-sterol and cholesterol acetate self-assemble into semicrystalline monolayers, bilayers, or trilayers on the surface of water, as has been reported previously. Here we have extended our thin film studies toward cholesteryl esters that, in their bulk crystals, pack as interdigitated bilayers due to the mismatch between the cross-sectional area of the rigid cholesterol moiety (40 Å2) and the attached hydrocarbon chain (20 Å2). As shown by grazing incidence X-ray diffraction (GIXD), cholesteryl esters spontaneously self-assemble on the surface of water in order to form interdigitated bilayer films. The unit cell parameters of such bilayers at the water surface almost match those of their three-dimensional counterparts. Other experiments such as surface pressure vs area per molecule isotherms and ellipsometry measurements corroborate this result. To control the growth of the interdigitated films, we have used “tailor-made” additives (long-chain alcohols or acids) that fill the voids in the chain region of the cholesteryl ester layer caused by the structural mismatch, thereby inhibiting interdigitation. Using this strategy, we were able to form a mixed monolayer composed of the ester and the additive molecules in a 1:1 ratio, where the hydrocarbon chain of additive molecule intercalates between the ester chains and effectively inhibits the growth of the interdigitated bilayer.
    No preview · Article · Aug 2001 · The Journal of Physical Chemistry B
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    Full-text · Conference Paper · Feb 2001
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    ABSTRACT: We have investigated the molecular conformations of a lipopolymer with a polyoxazoline headgroup at air/water interfaces as a function of lateral area per molecule with X-ray and neutron reflectometry. The polymer 1,2-dioctadecanyl-sn-glycero-3-poly(2-methyl-2-oxazoline), PMO−(C18)2, forms stable surface monolayers. Pressure/area isotherms around room temperature show a plateau region, indicative of a phase transition whose origin was examined. For data evaluation, a novel approach was used that acts on explicit quasi-molecular ensemble conformations of the polymer [Politsch et al., preceding paper in this issue]. At lower surface pressure, the polymer density distribution exhibits a maximum near the interface, indicative of attractive interaction between the predominantly hydrophilic polymer chains and the hydrophobic surface. Across the plateau region of the isotherm, a change in the volume density distribution of the alkyl chains was observed which is indicative of a partial immersion of the lipid moieties into the aqueous subphase. In contrast, no major structural change across the phase transition was detected in the polymer volume density profiles which comply with scaling predictions at both sides of the phase transition if deviations due to nonidealities are neglected. We interpret these observations as an alkyl chain ordering induced by the steric interference between the PMO:  Immersion of alkyl chains into the subphase relaxes the strain on the hydrophobic anchors which derives from a reduction of the configurational entropy of the PMO chains due to their confinement to the interface.
    Full-text · Article · Jan 2001 · Macromolecules
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    ABSTRACT: A new class of lipopolymers with polyoxazoline headgroups has been synthesized for the design of drug carriers, These amphiphatic molecules form stable monolayers at the air-water interface. Using X-ray and neutron reflectivity, the molecular conformations of the lipopolymer at the liquid surface were investigated as a function of surface pressure. The data are consistent with a fraction of the polyoxazoline moieties in brush-like conformations coexisting with a smaller fraction that is closely associated with the interface. Across the phase transition that is detected in the isotherm, the relative proportion between these two fractions is shifted. However, no qualitatively distinct molecular conformations are detected that would hint at a phase transition with respect to the polymer chains.
    Full-text · Article · Mar 2000 · Physica B Condensed Matter
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    ABSTRACT: Oriented crystalline monolayers, approximately 14 A thick, of a 2 x 2 Ag+ grid complex, self-assembled at the air-solution interface starting from an water-insoluble ligand 3,6-bis[2-(6-phenylpyridine)]pyridazine spread on silver-ion-containing solutions, were examined by grazing-incidence X-ray diffraction and specular X-ray reflectivity using synchrotron radiation. The monolayer structure was refined, including a determination of the positions of the counter-ions, with the SHELX-97 computer program. The monolayers were transferred from the interface onto various solid supports and visualized by scanning force microscopy, and characterized by X-ray photoelectron spectroscopy in terms of molecular structure. On surface compression, the initial self-assembled monolayer undergoes a transition to a crystalline bilayer in which the two layers, almost retaining the original arrangement, are in registry. Such a phase transition is of relevance to the understanding of crystal nucleation.
    Full-text · Article · Mar 2000 · Chemistry - A European Journal

Publication Stats

2k Citations
351.71 Total Impact Points

Institutions

  • 1995-2012
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 2006
    • Max Planck Institute for Molecular Genetics
      • Department of Human Molecular Genetics
      Berlín, Berlin, Germany
  • 1998
    • Max Planck Institute of Colloids and Interfaces
      • Department of Interfaces
      Potsdam, Brandenburg, Germany
    • Sultan Qaboos University
      Masqaţ, Masqaţ, Oman
  • 1994-1998
    • Weizmann Institute of Science
      • Department of Materials and Interfaces
      Rhovot, Central District, Israel
  • 1993
    • Iowa State University
      Ames, Iowa, United States
  • 1992
    • Johannes Gutenberg-Universität Mainz
      • Institute of Physical Chemistry
      Mayence, Rheinland-Pfalz, Germany
  • 1989-1990
    • Bar Ilan University
      • Department of Physics
      Gan, Tel Aviv, Israel